5-bromo-3-(3,4-dimethoxyphenyl)-1H-pyrrolo[2,3-b]pyridine | 1261082-88-5

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 吡咯
• 英文名称: 5-bromo-3-(3,4-dimethoxyphenyl)-1H-pyrrolo[2,3-b]pyridine
• CAS: 1261082-88-5
• 化学式: C₁₅H₁₃BrN₂O₂
• 分子量: 333.184
• InChiKey: CQTFWBDPOWQCQG-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  3.6
• 重原子数：
  20
• 可旋转键数：
  3
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.13
• 拓扑面积：
  47.1
• 氢给体数：
  1
• 氢受体数：
  3

反应信息

• 作为反应物：
  描述：

  5-bromo-3-(3,4-dimethoxyphenyl)-1H-pyrrolo[2,3-b]pyridine 在 (1,1'-bis(diphenylphosphino)ferrocene)palladium(II) dichloride 、 potassium carbonate 、 N,N-二异丙基乙胺 、 三氟乙酸 、 N-[(dimethylamino)-3-oxo-1H-1,2,3-triazolo[4,5-b]pyridin-1-yl-methylene]-N-methylmethanaminium hexafluorophosphate 作用下， 以 四氢呋喃 、 1,4-二氧六环 、 二氯甲烷 、 水 为溶剂， 反应 24.5h， 生成 4-((8-(4-(4-(3-(3,4-dimethoxyphenyl)-1H-pyrrolo[2,3-b]pyridin-5-yl)phenyl)piperazin-1-yl)-8-oxooctyl)amino)-2-(2,6-dioxopiperidin-3-yl)isoindoline-1,3-dione
  参考文献：
  名称：

  Discovery of highly efficient CRBN-recruiting HPK1-PROTAC as a potential chemical tool for investigation of scaffolding roles in TCR signaling

  摘要：

  DOI：

  10.1016/j.bioorg.2023.107016
• 作为产物：
  描述：

  5-溴-3-碘-7-氮杂吲哚 在 palladium bis[bis(diphenylphosphino)ferrocene] dichloride 、 potassium carbonate 、 三乙胺 作用下， 以 四氢呋喃 、 1,4-二氧六环 、 水 为溶剂， 反应 13.0h， 生成 5-bromo-3-(3,4-dimethoxyphenyl)-1H-pyrrolo[2,3-b]pyridine
  参考文献：
  名称：

  发现新型、有效、选择性和口服生物可利用的 HPK1 抑制剂，用于增强抗 PD-L1 抗体的功效

  摘要：

  造血祖细胞激酶 1 (HPK1) 是 MAP4K 家族中的一种丝氨酸/苏氨酸激酶，主要在免疫细胞中表达，并已被确定为免疫信号传导的负调节因子。越来越多的证据表明，HPK1 激酶功能的丧失可有效增强抗肿瘤反应。在这项研究中，我们从我们之前基于刚性化策略的工作开始，公开了发现有效、选择性和口服活性 HPK1 抑制剂的药物化学活动。系统构效关系 (SAR) 探索导致鉴定出 (。代表性化合物 , 表现出有效的 HPK1 抑制作用，IC 值为 1.39 nM，并对 TCR 相关激酶具有良好的选择性。此外，有效增强 IL Jurkat 细胞中分泌 -2（EC = 11.56 nM），治疗后观察到免疫逆转作用和改善的免疫反应。此外，与 -PD-L1 抗体联合显示出协同抗肿瘤功效，TGI% 值为 71.24 %。总的来说，我们的研究结果表明，CT26 模型可能是一种有价值的先导化合物，可用于开发安全有效的

  DOI：

  10.1016/j.ejmech.2024.116206

文献信息

• Structure-based de novo design and identification of D816V mutant-selective c-KIT inhibitors
  作者：Hwangseo Park、Soyoung Lee、Suhyun Lee、Sungwoo Hong

  DOI：10.1039/c4ob00053f

  日期：——

  New 7-azaindole-based c-KIT inhibitors with nanomolar inhibitory activity and high selectivity for the gain-of-function D816V mutant were identified through the structure-based de novo design using the scoring function improved by implementing an accurate solvation free energy.

  通过使用改进的精确溶剂自由能的评分函数进行基于结构的全新设计，确定了具有纳摩尔抑制活性和对功能获得性D816V突变体高选择性的新型7-氮杂吲哚基c-KIT抑制剂。

• 一种PROTACs分子及其应用
  申请人：杭州医学院

  公开号：CN117777125A

  公开（公告）日：2024-03-29

  本发明公开了一种式I结构的PROTAC化合物，及其在制备预防或治疗因T细胞受体信号通路相关蛋白(包括HPK1,LCK,GLK,PCKθ,ITK蛋白)的介导所引起的疾病的药物制剂中有所应用，如恶性肿瘤。#imgabs0#
• Development and Biological Evaluation of Potent and Selective c-KIT^D816V Inhibitors
  作者：Soyoung Lee、Hyunseung Lee、Jinhee Kim、Suhyun Lee、Soo Jung Kim、Byong-Seok Choi、Soon-Sun Hong、Sungwoo Hong

  DOI：10.1021/jm500413g

  日期：2014.8.14

  The c-KIT tyrosine kinase has emerged as a potential therapeutic target for an array of diseases. However, there exists a drug resistance that is caused by mutations in c-KIT; therefore, c-KIT remains as a clinical challenge due to limited effective treatment options for therapies. For example, the acquired activating point mutation D816V significantly impairs the efficacy of targeted cancer therapies. Understanding the mechanisms of drug resistance at the molecular level will aid in designing and developing particular inhibitors with the potential to overcome these resistance mutations. We undertake a structure-based de novo design of 7-azaindole as the molecular core using the modified scoring function. This approach led to an identification of new c-KIT inhibitors over 100-fold specific for the D816V mutant relative to the wild-type c-KIT with nanomolar inhibitory activity. More importantly, these compounds potently inhibit clinically relevant D816V mutations of c-KIT in biochemical and cellular studies.
• Design, Synthesis, and Evaluation of 3,5-Disubstituted 7-Azaindoles as Trk Inhibitors with Anticancer and Antiangiogenic Activities
  作者：Seunghee Hong、Jinhee Kim、Ju Hyeon Seo、Kyung Hee Jung、Soon-Sun Hong、Sungwoo Hong

  DOI：10.1021/jm3002982

  日期：2012.6.14

  Tropomyosin-related kinase A (TrkA) is considered a promising target in the development of a therapeutic treatment of cancer and pain. In this study, we designed and synthesized a series of novel 7-azaindole-based Trk kinase inhibitors through the structure-based design strategy. By varying the functional groups at the 3 and 5 positions of a 7-azaindole scaffold, we studied the structure-activity relationships (SAR) profiles and identified a series of potent Trk inhibitors. Representative derivatives showed desirable activity in cellular proliferation and apoptosis assays. Moreover, these inhibitors exhibited noteworthy antiangiogenic activity.
• Discovery of new azaindole-based PI3Kα inhibitors: Apoptotic and antiangiogenic effect on cancer cells
  作者：Seunghee Hong、Soyoung Lee、Bomi Kim、Hyunseung Lee、Soon-Sun Hong、Sungwoo Hong

  DOI：10.1016/j.bmcl.2010.10.108

  日期：2010.12

  Phosphatidylinositol-3-kinase alpha (PI3K alpha) is an important target in cancer due to the deregulation of the PI3K/AKT signaling pathway in many tumors. In this study, we designed [3,5-d]-7-azaindole analogs as PI3K alpha inhibitors through the fragment-growing strategy. By varying groups at the 3,5-positions of azaindole, we developed the SAR (Structure-activity relationship) and identified a series of potent PI3K alpha inhibitors. Representative azaindole derivatives showed activity in a cellular proliferation and apoptosis assays. Moreover, B3 exhibited strong antiangiogenic effects on cancer cells. (C) 2010 Elsevier Ltd. All rights reserved.